Project Summary Stress-related disorders, such as generalized anxiety and post-traumatic stress disorder, are widespread, affecting over one quarter of the human population. Whereas much is known about how the brain drives stress responses, little is known about neuronal mechanisms that restore baseline states of behavior and physiology once the stressor has been evaded or removed. Nonetheless, recent studies suggest that dysfunction of neuronal mechanisms that promote recovery may underlie the etiology of stress-related disorders. We have devised a novel approach to examine neuronal systems modulating stress recovery using zebrafish, and have identified the dorsal habenular nuclei (dHb) as a central regulator of stress recovery. We over, we have found that neuronal activity in the extended amygdala of fish also corresponds to recovery, suggesting a brain-wide extended-amygdala to dHb circuit underlying stress recovery. The experiments outlined in this proposal will perform a genetic dissection of this circuit that modulates stress recovery. Using two-photon, whole brain imaging, we will also determine how this circuit fits into a larger, brain-wide circuit modulating recovery. The proposed experiments will reveal critical insight into how the brain modulates recovery, a poorly understood facet of the stress response. Moreover, because physiology and neuroanatomy are largely conserved between zebrafish and mammals, the findings in this study may further our understanding and aid in the treatment of stress-related disorders.